tbuckley/cabot-search huggingface dataset:
Alterations of cohesin complex genes in acute myeloid leukemia: differential co-mutations, clinical presentation and impact on outcome
Authors: Jan-Niklas Eckardt, Sebastian Stasik, Christoph Röllig, Tim Sauer, Sebastian Scholl, Andreas Hochhaus, Martina Crysandt, Tim H. Brümmendorf, Ralph Naumann, Björn Steffen, Volker Kunzmann, Hermann Einsele, Markus Schaich, Andreas Burchert, Andreas Neubauer, Kerstin Schäfer-Eckart, Christoph Schliemann, Stefan W. Krause, Regina Herbst, Mathias Hänel, Maher Hanoun, Ulrich Kaiser, Martin Kaufmann, Zdenek Rácil, Jiri Mayer, Tiago Cerqueira, Frank Kroschinsky, Wolfgang E. Berdel, Hubert Serve, Carsten Müller-Tidow, Uwe Platzbecker, Claudia D. Baldus, Johannes Schetelig, Timo Siepmann, Martin Bornhäuser, Jan Moritz Middeke, Christian Thiede
Journal: Blood Cancer Journal (2023)

Functional perturbations of the cohesin complex with subsequent changes in chromatin structure and replication are reported in a multitude of cancers including acute myeloid leukemia (AML). Mutations of its STAG2 subunit may predict unfavorable risk as recognized by the 2022 European Leukemia Net recommendations, but the underlying evidence is limited by small sample sizes and conflicting observations regarding clinical outcomes, as well as scarce information on other cohesion complex subunits. We retrospectively analyzed data from a multi-center cohort of 1615 intensively treated AML patients and identified distinct co-mutational patters for mutations of STAG2, which were associated with normal karyotypes (NK) and concomitant mutations in IDH2, RUNX1, BCOR, ASXL1, and SRSF2. Mutated RAD21 was associated with NK, mutated EZH2, KRAS, CBL, and NPM1. Patients harboring mutated STAG2 were older and presented with decreased white blood cell, bone marrow and peripheral blood blast counts. Overall, neither mutated STAG2, RAD21, SMC1A nor SMC3 displayed any significant, independent effect on clinical outcomes defined as complete remission, event-free, relapse-free or overall survival. However, we found almost complete mutual exclusivity of genetic alterations of individual cohesin subunits. This mutual exclusivity may be the basis for therapeutic strategies via synthetic lethality in cohesin mutated AML.
Should lipoprotein(a) be routinely measured after <scp>COVID</scp>‐19? Comment on the article by Stahl et al
Authors: Dimitrios Patoulias, Athina Dimosiari, Theodoros Michailidis
Journal: Arthritis & Rheumatology (2023)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Sequencing <scp>antigen‐targeting</scp> antibodies and cellular therapies in adults with relapsed/refractory <scp>B‐cell</scp> acute lymphoblastic leukemia
Authors: Ibrahim Aldoss, Bijal D. Shah, Jae H. Park, Lori Muffly, Aaron C. Logan, Patrick Brown, Wendy Stock, Elias J. Jabbour
Journal: American Journal of Hematology (2023)

The recent approvals of four CD19-or CD22-targeted therapies for B-cell acute lymphoblastic leukemia (B-ALL) have transformed the treatment of relapsed/refractory (r/r) disease. Adults with r/r B-ALL are usually eligible for all options, but there are no studies directly comparing these agents, and the treating physician must decide which to select. Each therapy has notable activity as a single agent but has limitations in particular settings, and the optimal choice varies. These therapies can be complementary and used either sequentially or concomitantly. Here, we review the current landscape of antigen-targeted therapies for r/r B-ALL and discuss considerations for their use.
Photosensitive and Conductive Hydrogel Induced Innerved Bone Regeneration for Infected Bone Defect Repair (Adv. Healthcare Mater. 3/2023)
Authors: Xirui Jing, Chao Xu, Weijie Su, Qiuyue Ding, Bing Ye, Yanlin Su, Keda Yu, Lian Zeng, Xu Yang, Yanzhen Qu, Kaifang Chen, Tingfang Sun, Zhiqiang Luo, Xiaodong Guo
Journal: Advanced Healthcare Materials (2023)
CSL324, a granulocyte colony-stimulating factor receptor antagonist, blocks neutrophil migration markers that are upregulated in hidradenitis suppurativa
Authors: Cristina Gamell, Aleksandra Bankovacki, Karen Scalzo-Inguanti, Bradley Sedgmen, Monther Alhamdoosh, Emma Gail, Lydia Turkovic, Christine Millar, Laura Johnson, Michelle Wahlsten, Jim Richter, Jared Schuster, Allison Dyson, Jenny Nicolopoulos, George Varigos, Milica Ng, Nick Wilson, Judith Field, Johannes S Kern, Lisa M Lindqvist
Journal: British Journal of Dermatology (2023)

Abstract Background Neutrophils have been shown to contribute to the pathophysiology of hidradenitis suppurativa (HS), a chronic, painful and debilitating inflammatory skin disease, yet their exact role remains to be fully defined. Granulocyte colony-stimulating factor (G-CSF), a major regulator of neutrophil development and survival, can be blocked by the novel, fully human anti-G-CSF receptor (G-CSFR) monoclonal antibody CSL324. Objectives We investigated the activation and migration of neutrophils in HS and the impact of blocking G-CSFR with CSL324. Methods Biopsy and peripheral blood samples were taken from participants of two studies: 2018.206, a noninterventional research study of systemic and dermal neutrophils and inflammatory markers in patients with neutrophilic skin diseases, and CSL324_1001 (ACTRN12616000846426), a single-dose ascending and repeated dose, randomized, double-blind, placebo-controlled study to assess the safety, pharmacokinetics and pharmacodynamics of CSL324 in healthy adult subjects. Ex vivo experiments were performed, including neutrophil enumeration and immunophenotyping, migration, receptor occupancy and transcriptome analysis. Results The number of cells positive for the neutrophil markers myeloperoxidase (MPO) and neutrophil elastase (NE) was significantly higher in HS lesions compared with biopsies from healthy donors (HDs) (P &amp;lt; 0.0001 and P = 0.0223, respectively). In peripheral blood samples, mean neutrophil counts were significantly higher in patients with HS than in HDs (2.98 vs. 1.60 × 109 L–1, respectively; P = 8.8 × 10–4). Neutrophil migration pathways in peripheral blood were increased in patients with HS and their neutrophils demonstrated an increased migration phenotype, with higher mean CXCR1 on the surface of neutrophils in patients with HS (24453.20 vs. 20798.47 for HD; P = 0.03). G-CSF was a key driver of the transcriptomic changes in the peripheral blood of patients with HS and was elevated in serum from patients with HS compared with HDs (mean 6.61 vs. 3.84 pg mL–1, respectively; P = 0.013). Administration of CSL324 inhibited G-CSF-induced transcriptional changes in HDs, similar to those observed in the HS cohort, as highlighted by expression changes in genes related to neutrophil migratory capacity. Conclusions Data suggest that neutrophils contribute to HS pathophysiology and that neutrophils are increased in lesions due to an increase in G-CSF-driven migration. CSL324 counteracted G-CSF-induced transcriptomic changes and blocked neutrophil migration by reducing cell-surface levels of chemokine receptors.
The mechanism underlying redundant functions of the YTHDF proteins
Authors: Zhongyu Zou, Caraline Sepich-Poore, Xiaoming Zhou, Jiangbo Wei, Chuan He
Journal: Genome biology (2023)

Abstract The YTH N 6 -methyladenosine RNA binding proteins (YTHDFs) mediate the functional effects of N 6 -methyladenosine (m 6 A) on RNA. Recently, a report proposed that all YTHDFs work redundantly to facilitate RNA decay, raising questions about the exact functions of individual YTHDFs, especially YTHDF1 and YTHDF2. We show that YTHDF1 and YTHDF2 differ in their low-complexity domains (LCDs) and exhibit different behaviors in condensate formation and subsequent physiological functions. Biologically, we also find that the global stabilization of RNA after depletion of all YTHDFs is driven by increased P-body formation and is not strictly m 6 A dependent.
Homeostatic, Non-Canonical Role of Macrophage Elastase in Vascular Integrity
Authors: Mani Salarian, Mean Ghim, Jakub Toczek, Jinah Han, Dar Weiss, Bart Spronck, Abhay B. Ramachandra, Jae-Joon Jung, Gunjan Kukreja, Jiasheng Zhang, Deaneira Lakheram, Sung-Kwon Kim, Jay D. Humphrey, Mehran M. Sadeghi
Journal: Circulation Research (2023)

Matrix metalloproteinase (MMP)-12 is highly expressed in abdominal aortic aneurysms and its elastolytic function has been implicated in the pathogenesis. This concept is challenged, however, by conflicting data. Here, we sought to revisit the role of MMP-12 in abdominal aortic aneurysm.Apoe-/- and Mmp12-/-/Apoe-/- mice were infused with Ang II (angiotensin). Expression of neutrophil extracellular traps (NETs) markers and complement component 3 (C3) levels were evaluated by immunostaining in aortas of surviving animals. Plasma complement components were analyzed by immunoassay. The effects of a complement inhibitor, IgG-FH1-5 (factor H-immunoglobulin G), and macrophage-specific MMP-12 deficiency on adverse aortic remodeling and death from rupture in Ang II-infused mice were determined.Unexpectedly, death from aortic rupture was significantly higher in Mmp12-/-/Apoe-/- mice. This associated with more neutrophils, citrullinated histone H3 and neutrophil elastase, markers of NETs, and C3 levels in Mmp12-/- aortas. These findings were recapitulated in additional models of abdominal aortic aneurysm. MMP-12 deficiency also led to more pronounced elastic laminae degradation and reduced collagen integrity. Higher plasma C5a in Mmp12-/- mice pointed to complement overactivation. Treatment with IgG-FH1-5 decreased aortic wall NETosis and reduced adverse aortic remodeling and death from rupture in Ang II-infused Mmp12-/- mice. Finally, macrophage-specific MMP-12 deficiency recapitulated the effects of global MMP-12 deficiency on complement deposition and NETosis, as well as adverse aortic remodeling and death from rupture in Ang II-infused mice.An MMP-12 deficiency/complement activation/NETosis pathway compromises aortic integrity, which predisposes to adverse vascular remodeling and abdominal aortic aneurysm rupture. Considering these new findings, the role of macrophage MMP-12 in vascular homeostasis demands re-evaluation of MMP-12 function in diverse settings.
Apolipoprotein Proteomics for Residual Lipid-Related Risk in Coronary Heart Disease
Authors: Robert Clarke, Adam Von Ende, Lukas E. Schmidt, Xiaoke Yin, Michael Hill, Alun D. Hughes, Raimund Pechlaner, Johann Willeit, Stefan Kiechl, Hugh Watkins, Konstantinos Theofilatos, Jemma C. Hopewell, Manuel Mayr
Journal: Circulation Research (2023)

Background: Recognition of the importance of conventional lipid measures and the advent of novel lipid-lowering medications have prompted the need for more comprehensive lipid panels to guide use of emerging treatments for the prevention of coronary heart disease (CHD). This report assessed the relevance of 13 apolipoproteins measured using a single mass-spectrometry assay for risk of CHD in the PROCARDIS case-control study of CHD (941 cases/975 controls). Methods: The associations of apolipoproteins with CHD were assessed after adjustment for established risk factors and correction for statin use. Apolipoproteins were grouped into 4 lipid-related classes [lipoprotein(a), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides] and their associations with CHD were adjusted for established CHD risk factors and conventional lipids. Analyses of these apolipoproteins in a subset of the ASCOT trial (Anglo-Scandinavian Cardiac Outcomes Trial) were used to assess their within-person variability and to estimate a correction for statin use. The findings in the PROCARDIS study were compared with those for incident cardiovascular disease in the Bruneck prospective study (n=688), including new measurements of Apo(a). Results: Triglyceride-carrying apolipoproteins (ApoC1, ApoC3, and ApoE) were most strongly associated with the risk of CHD (2- to 3-fold higher odds ratios for top versus bottom quintile) independent of conventional lipid measures. Likewise, ApoB was independently associated with a 2-fold higher odds ratios of CHD. Lipoprotein(a) was measured using peptides from the Apo(a)-kringle repeat and Apo(a)-constant regions, but neither of these associations differed from the association with conventionally measured lipoprotein(a). Among HDL-related apolipoproteins, ApoA4 and ApoM were inversely related to CHD, independent of conventional lipid measures. The disease associations with all apolipoproteins were directionally consistent in the PROCARDIS and Bruneck studies, with the exception of ApoM. Conclusions: Apolipoproteins were associated with CHD independent of conventional risk factors and lipids, suggesting apolipoproteins could help to identify patients with residual lipid-related risk and guide personalized approaches to CHD risk reduction.
Author Correction: Randomization, design and analysis for interdependency in aging research: no person or mouse is an island
Authors: Daniella E. Chusyd, Steven N. Austad, Stephanie L. Dickinson, Keisuke Ejima, Gary L. Gadbury, Lilian Golzarri-Arroyo, Richard J. Holden, Yasaman Jamshidi-Naeini, Doug Landsittel, Tapan Mehta, J. Michael Oakes, Arthur H. Owora, Greg Pavela, Javier Rojo, Michael W. Sandel, Daniel L. Smith, Colby J. Vorland, Pengcheng Xun, Roger Zoh, David B. Allison
Journal: Nature Aging (2023)
Why I . . . own a vintage campervan
Authors: Kathy Oxtoby
Journal: BMJ (2023)

As the storm raged on, the military tanks rolled by, and the shells continued to fire past him, GP Paul Reynolds reflected that this was not the relaxing getaway he'd hoped for.But by then he had learnt that life on the road with Clementine meant expecting the unexpected.Clementine the campervan-
177Lu-rhPSMA-10.1 Induces Tumor Response in a Patient With mCRPC After PSMA-Directed Radioligand Therapy With 177Lu-PSMA-I&amp;T
Authors: Ralph A. Bundschuh, Christian H. Pfob, Georgine Wienand, Alexander Dierks, Malte Kircher, Constantin Lapa
Journal: Clinical Nuclear Medicine (2023)

177 Lu-rhPSMA-10.1 is a novel PSMA-targeting radiopharmaceutical that has been optimized in terms of pharmacological and pharmacokinetic properties and may be therefore advantageous in treatment of metastatic castrate-resistant prostate cancer. In this image, we present the case of an 86-year-old man with metastastic castrate-resistant prostate cancer undergoing 177 Lu-PSMA-I&T treatment. After initial partial response to radioligand therapy, another 2 treatment cycles resulted in a rising serum PSA level that could be correlated with increasingly PSMA-positive as well as a new bone lesion. Consequently, the patient was changed to 177 Lu-rhPSMA-10.1 treatment on a compassionate use basis achieving a renewed tumor response.
Interesting Findings in 68Ga-FAPI-46 PET/CT Imaging in a Patient With Glioblastoma Multiforme
Authors: Hadis Mohammadzadeh Kosari, Zahra Kiamanesh, Ramin Sadeghi, Hassan Kamali, Kamran Aryana
Journal: Clinical Nuclear Medicine (2023)

Abstract A 55-year-old disabled man with glioblastoma multiforme was referred to us for fibroblast activation protein inhibitor (FAPI) PET/CT imaging. 68 Ga-DOTA-FAPI-46 scan revealed uptake in the primary tumor and unexpected uptakes in soft tissue, especially in periarticular regions. These latter foci were compatible with calcifications on the CT. One in the breast was compatible with fibrotic tissue, but 2 other foci, in the rectus abdominis and gallbladder wall, could not be correlated with the CT findings. In Neurogenic heterotopic ossification, hypoxia-associated oxidative stress results in the metaplastic transformation of fibroblasts. Abnormal differentiation of fibroblasts in neurogenic heterotopic ossification before ossification could explain radiolabeled FAPI avidity in the mentioned areas.
The cost and cost-effectiveness of novel tuberculosis vaccines in low- and middle-income countries: A modeling study
Authors: Allison Portnoy, Rebecca A. Clark, Matthew Quaife, Chathika K. Weerasuriya, Christinah Mukandavire, Roel Bakker, Arminder K. Deol, Shelly Malhotra, Nebiat Gebreselassie, Matteo Zignol, So Yoon Sim, Raymond C. W. Hutubessy, Inés Garcia Baena, Nobuyuki Nishikiori, Mark Jit, Richard G. White, Nicolas A. Menzies
Journal: PLoS Medicine (2023)

Tuberculosis (TB) is preventable and curable but eliminating it has proven challenging. Safe and effective TB vaccines that can rapidly reduce disease burden are essential for achieving TB elimination. We assessed future costs, cost-savings, and cost-effectiveness of introducing novel TB vaccines in low- and middle-income countries (LMICs) for a range of product characteristics and delivery strategies.
α<sub>v</sub>β<sub>6</sub> Integrin Positron Emission Tomography of Lung Fibrosis in Idiopathic Pulmonary Fibrosis and Long COVID-19
Authors: Richard H. Kimura, Husham Sharifi, Bin Shen, Gerald J. Berry, H. Henry Guo
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"αvβ6 Integrin Positron Emission Tomography of Lung Fibrosis in Idiopathic Pulmonary Fibrosis and Long-COVID." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Low-Flow Inflation Pressure–Time Curve to Identify Airway Opening Pressure in a Patient Receiving Venovenous Extracorporeal Membrane Oxygenation
Authors: Manuel Tisminetzky, Bruno L. Ferreyro, Michael C. Sklar, Lu Chen, Shaf Keshavjee, Marcelo Cypel, Eddy Fan, Niall D. Ferguson, Laurent Brochard, Ghislaine Douflé, Lorenzo Del Sorbo
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Low-Flow Inflation Pressure-Time Curve to Identify Airway Opening Pressure in a Patient on Veno-Venous ECMO." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
My Journey
Authors: Lucy Balian Rorke-Adams
Journal: Annual Review of Pathology Mechanisms of Disease (2023)

This is the life story of Dr. Lucy B. Rorke-Adams, who was raised in the rural Midwest of the United States by Armenian immigrant parents during the Depression. The youngest in a family of five girls, she was lovingly nurtured by her parents and sisters. She was encouraged to become educated in order to lead a worthwhile life and contribute to society. She chose medicine, specifically the specialty of pediatric neuropathology, and over her long career succeeded in advancing the field. In particular, she made major contributions to understanding childhood brain tumors, central nervous system (CNS) malformations, and pathophysiology of abusive CNS injury in infants and children.
Quantifying the Relationship Between Physical Activity Energy Expenditure and Incident Type 2 Diabetes: A Prospective Cohort Study of Device-Measured Activity in 90,096 Adults
Authors: Tessa Strain, Paddy C. Dempsey, Katrien Wijndaele, Stephen J. Sharp, Nicola Kerrison, Tomas I. Gonzales, Chunxiao Li, Eleanor Wheeler, Claudia Langenberg, Søren Brage, Nick Wareham
Journal: Diabetes Care (2023)

OBJECTIVE To investigate the association between accelerometer-derived physical activity energy expenditure (PAEE) and incident type 2 diabetes (T2D) in a cohort of middle-aged adults and within subgroups. RESEARCH DESIGN AND METHODS Data were from 90,096 UK Biobank participants without prevalent diabetes (mean 62 years of age; 57% women) who wore a wrist accelerometer for 7 days. PAEE was derived from wrist acceleration using a population-specific method validated against doubly labeled water. Logistic regressions were used to assess associations between PAEE, its underlying intensity, and incident T2D, ascertained using hospital episode and mortality data up to November 2020. Models were progressively adjusted for demographic, lifestyle factors, and BMI. RESULTS The association between PAEE and T2D was approximately linear (n = 2,018 events). We observed 19% (95% CI 17–21) lower odds of T2D per 5 kJ · kg−1 · day−1 in PAEE without adjustment for BMI and 11% (9–13) with BMI adjustment. The association was stronger in men than women and weaker in those with obesity and higher genetic susceptibility to obesity. There was no evidence of effect modification by genetic susceptibility to T2D or insulin resistance. For a given level of PAEE, odds of T2D were lower among those engaging in more moderate-to-vigorous activity. CONCLUSIONS There was a strong linear relationship between PAEE and incident T2D. A difference in PAEE equivalent to an additional daily 20-min brisk walk was associated with 19% lower odds of T2D. The association was broadly similar across population subgroups, supporting physical activity for diabetes prevention in the whole population.
Reply to Dutkiewicz and Mackiewicz
Authors: Ganesh Raghu, Martina Koziar Vasakova, Kevin C. Wilson
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to: Hypersensitivity Pneumonitis: Correct Identification of Causative Microbial Agents Is Essential for Efficient Diagnosis and Prevention." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Hepatocellular Carcinoma ≤5 cm: Biological Characteristics and Patient Outcomes
Authors: Wen-Jia Cai, Minghua Ying, Rong-Qin Zheng, Jintang Liao, Baoming Luo, Lina Tang, Wen Cheng, Hong Yang, An Wei, Yilin Yang, Hui Wang, Yan-Chun Luo, Cun Liu, Hui Zhong, Qi Yang, Jie Yu, Ping Liang
Journal: Liver Cancer (2023)

The present study aimed to evaluate the influence of biological characteristics of hepatocellular carcinoma (HCC) on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasound (CEUS) in patients with high risk and compare the outcomes among different categories after radical resection.Between June 2017 and December 2020, standardized CEUS data of liver nodules were prospectively collected from multiple centers across China. We conducted a retrospective analysis of the prospectively collected data on HCCs measuring no more than 5 cm, as diagnosed by pathology. LI-RADS categories were assigned after thorough evaluation of CEUS features. Then, CEUS LI-RADS categories and major features were compared in different differentiation, Ki-67, and microvascular invasion (MVI) statuses. Differences in recurrence-free survival (RFS) among different LI-RADS categories were further analyzed.A total of 293 HCC nodules in 293 patients were included. This study revealed significant differences in the CEUS LI-RADS category of HCCs among differentiation (p < 0.001) and levels of Ki-67 (p = 0.01) and that poor differentiation (32.7% in LR-M, 12% in LR-5, and 6.2% in LR-4) (p < 0.001) and high level of Ki-67 (median value 30%) were more frequently classified into the LR-M category, whereas well differentiation (37.5% in LR-4, 15.1% in LR-5, and 11.5% in LR-M) and low levels of Ki-67 (median value 11%) were more frequently classified into the LR-4 category. No significant differences were found between MVI and CEUS LI-RADS categories (p > 0.05). With a median follow-up of 23 months, HCCs assigned to different CEUS LI-RADS classes showed no significant differences in RFS after resection.Biological characteristics of HCC, including differentiation and level of Ki-67 expression, could influence major features of CEUS and impact the CEUS LI-RADS category. HCCs in different CEUS LI-RADS categories showed no significant differences in RFS after resection.
Treatment of Obstructive Sleep Apnea and Diabetic Kidney Disease: Can Continuous Positive Airway Pressure Reduce Albuminuria Progression?
Authors: Yating Chen, Riken Chen, Yiqi Lin, Jianxiong Lai, Jiahe Wang, Xiaofeng Zhu, Yinghua Liu, Zhuofan Zhang, Yuhan Yang, Dongxing Zhao
Journal: American Journal of Respiratory and Critical Care Medicine (2023)
Hypersensitivity Pneumonitis: Correct Identification of Causative Microbial Agents Is Essential for Efficient Diagnosis and Prevention
Authors: Jacek Dutkiewicz, Barbara Mackiewicz
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Hypersensitivity Pneumonitis: Correct Identification of Causative Microbial Agents Is Essential for Efficient Diagnosis and Prevention ." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –